Next Generation ORS: Controlled Trial Comparing ORS With Calcium vs Standard ORS in Reducing Severity of Acute Watery Diarrhea

University of Florida

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Cholera; Diarrhea

Treatments: Drug: Next Generation ORS (oral rehydration solution) (including placebo; Drug: Current standard control ORS (oral rehydration solution)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05814042

1R21AI169282-01A1 (U.S. NIH Grant/Contract)

IRB202202746 -N -R

Details and patient eligibility

About

Diarrhea remains a leading killer of children in need of better treatments.

Full description

Diarrhea remains a leading killer of children in need of better treatments. Oral Rehydration Solution (ORS) is currently the only oral therapy that is recommended for children with acute diarrhea. Although it is valuable for correcting dehydration and is considered the primary reason for the substantial reduction in mortality from diarrhea in children, ORS does not have the capacity to "halt" intestinal fluid loss and thus, does not offer a rapid relief of a child's diarrhea symptom, and its use by caregivers and medical practitioners has markedly dropped (estimate use in 1/3 of cases who need it). In recognition of its limitations, continuous efforts have been made to modify the composition of ORS. However, none has targeted the central diarrhea-causing pathways and produced a satisfactory outcome in children. New therapeutic approaches and methods are needed. The proposed new ORS is based on recent discovery of the first inclusive antidiarrheal mechanism in the intestine, CaSR (calcium-sensing receptor) that targets all known diarrhea causing pathways. It works in animals. This R21 is the 1st proof-of-concept clinical study in humans and is intended to investigate its safety and efficacy. Two Specific Aims are proposed to determine new ORS safety and efficacy in patients with diarrhea. In the safety study, the investigators propose to enroll 396 diarrheal adults (198 in Intervention New ORS group and 198 in standard WHO ORS). In the efficacy study, the investigators plan to enroll 396 diarrheal adults (198 in Intervention New ORS group and 198 in standard WHO ORS, these will be same patients employed for the safety study). These diarrheal patients will be recruited from the Dhaka area in Bangladesh. At the conclusion of the study, we expect to develop a novel oral rehydrating solution that is inexpensive and practical to use in all the countries. Hypothesis: the volume output Intervention should reduce stool weight/output of diarrhea by 30%.

Enrollment: 396 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult male and female patients, age between 18 and 60 years, history of acute watery diarrhea (defined as the passage of ≥3 loose or watery stools in the past 24 hours) for less than 24 h before admission, either signs of severe dehydration and stool positive for Vibrio cholerae, and successful rehydration with intravenous fluids within the first 6 h after admission (cholera group), or signs of some dehydration and stool negative for V. cholera (non-cholera group) , and successful rehydration with intravenous or oral fluids within the first 6 h

Exclusion criteria

• Pregnancy as determined by history of last menstrual period, bloody diarrhea, signs of systemic infection that needed intravenous antibiotics, or inability to rehydrate with intravenous fluid therapy in the first 6 h after admission.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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396 participants in 2 patient groups

Nutrient based intervention

Experimental group

Description:

Nutrition supplement used to stop diarrhea

Treatment:

Drug: Next Generation ORS (oral rehydration solution) (including placebo

Standard of Care oral rehydration solution

Active Comparator group

Description:

Standard of care nutrition supplement used to stop diarrhea.

Treatment:

Drug: Current standard control ORS (oral rehydration solution)